Cell surfaces.

Anderson, Mary R.

doi:10.1038/bjc.1966.38

Cited by 3 publications

(4 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Introductionmentioning

confidence: 99%

“…Empirical evidence generated over 5 decades demonstrates that cells undergo structural changes at the molecular level in response to environmental cues that change cell-surface and cell-receptor interactions with their ligands, leading to a modified cell state. 1,2 Owing to their accessibility, membrane proteins remain the most attractive targets in developing molecular therapeutic tools. However, when cell membrane proteins are purified, their resultant conformation can be very different from that in their native state, thus making cell-surface proteins challenging as targets for the development of artificial ligands, drugs, or diagnostics.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Integrating Ligand-Receptor Interactions and In Vitro Evolution for Streamlined Discovery of Artificial Nucleic Acid Ligands

Zumrut

Batool

Argyropoulos

et al. 2019

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

To discover DNA ligands against a predetermined receptor protein complex, we introduce a comprehensive version of ligand-guided selection (LIGS). LIGS is, itself, a variant of systematic evolution of ligands by exponential enrichment (SELEX). Herein, we have optimized LIGS to identify higher affinity aptamers with high specificity. In addition, we demonstrate the expandability of LIGS by performing specific aptamer elution at 25°C, utilizing multiple monoclonal antibodies (mAbs) against cultured cells and primary cells obtained from human donors expressing the same receptor. Eluted LIGS libraries obtained through Illumina high-throughput (HT) DNA sequencing were analyzed by bioinformatics tools to discover five DNA aptamers with apparent affinities ranging from 3.06 ± 0.485 nM to 325 ± 62.7 nM against the target, T cell receptor-cluster of differentiation epsilon (TCR-CD3ε) expressed on human T cells. The specificity of the aptamers was validated utilizing multiple strategies, including competitive binding analysis and a double-knockout Jurkat cell line generated by CRISPR technology. The cross-competition experiments using labeled and unlabeled aptamers revealed that all five aptamers compete for the same binding site. Collectively, the data in this report introduce a modified LIGS strategy as a universal platform to identify highly specific multiple aptamers toward multi-component receptor proteins in their native state without changing the cell-surface landscape.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrating Ligand-Receptor Interactions and In Vitro Evolution for Streamlined Discovery of Artificial Nucleic Acid Ligands

Zumrut

Batool

Argyropoulos

et al. 2019

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“…Cells regularly respond to their surroundings and differentially express cell surface receptors in response to environmental cues. − Any perturbation of endogenous interactions between cell surface receptors and their ligands could transform the cell, leading to an altered cellular state. Because of their significant role in maintaining the cell’s physiological state, approximately 60% of current drugs on the market are directed against cell surface receptors .…”

Section: Introductionmentioning

confidence: 99%

Ligand Guided Selection (LIGS) of Artificial Nucleic Acid Ligands against Cell Surface Targets

Zumrut

Mallikaratchy

2019

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

With the success of RNA-based therapeutic drugs, the demand has increased for sophisticated nucleic-acid-based targeting agents. Nucleic acid aptamers (NAAs), in this regard, represent a suitable class of molecules with synthetic versatility. Aptamers are composed of single-stranded RNA/DNA/XNA molecules, which can be identified using a method called systematic evolution of ligands by exponential enrichment (SELEX) against any molecule. This Spotlight summarizes the recent introduction of ligand guided selection (LIGS), which will permit the identification of a wide range of functional aptamers against complex targets such as cell surface receptors while maintaining their native functional state. Aptamers identified from LIGS will allow researchers to develop aptamers in biomedicine as low-cost, stable therapeutic agents and diagnostic molecules or biochemical devices.

show abstract

“…More than 50 years ago, researchers began to speculate that cell surface molecules respond to external stimuli and perhaps undergo modification at the membrane level [ 1 ]. Indeed, considerable empirical evidence over the years has demonstrated that the cell surface does undergo structural changes at the molecular level in response to either external or internal stimuli and that such changes lead to alterations in cell signaling and transforming the function of a cell [ 2 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Engineered Aptamers to Probe Molecular Interactions on the Cell Surface

et al. 2017

View full text Add to dashboard Cite

Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds that function as modulators of cell membrane events must be coupled to a targeting moiety with superior chemical versatility. In this regard, nucleic acid aptamers are a suitable class of targeting moieties. Aptamers are inherently chemical in nature, allowing extensive site-specific chemical modification to engineer sensing molecules. Aptamers can be easily selected using a simple laboratory-based in vitro evolution method enabling the design and development of aptamer-based functional molecular scaffolds against wide range of cell surface molecules. This article reviews the application of aptamers as monitors and modulators of molecular interactions on the mammalian cell surface with the aim of increasing our understanding of cell-surface receptor response to external stimuli. The information gained from these types of studies could eventually prove useful in engineering improved medical diagnostics and therapeutics.

show abstract

Cell surfaces.

Cited by 3 publications

References 19 publications

Integrating Ligand-Receptor Interactions and In Vitro Evolution for Streamlined Discovery of Artificial Nucleic Acid Ligands

Integrating Ligand-Receptor Interactions and In Vitro Evolution for Streamlined Discovery of Artificial Nucleic Acid Ligands

Ligand Guided Selection (LIGS) of Artificial Nucleic Acid Ligands against Cell Surface Targets

Engineered Aptamers to Probe Molecular Interactions on the Cell Surface

Contact Info

Product

Resources

About